These studies seek to define and describe the molecular mechanisms whereby the major catabolic (i.e. energy-releasing) pathways of intermediary metabolism are controlled, and to investigate the ways in which these controls are altered in old-age. Such alterations are considered to underlie the decreased ability of senescent animals (including humans) to withstand environmental stresses (e.g. starvation, severe cold). Current investigations emphasize: (1) the role of mitochondrial Ca++ transport in the control of pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase in cardiac and skeletal muscles and brain; (2) the impact of aging upon the activity of mitochondrial Ca++ transport, both uptake and release, in a variety of tissues, viz: skeletal muscle, brain, kidney and liver; (3) the effect of fatty acid and ketone oxidation on the oxidation of pyruvate, and the activity of pyruvate dehydrogenase, in skeletal muscle mitochondria; and (4) the effect of aging upon the transport of acylcarnitine species into skeleta muscle mitochondria.